Department of Psychology, Integrative Neuroscience Program, Stony Brook University, Stony Brook, NY, USA.
Department of Neurology, Stony Brook University, Stony Brook, NY, USA.
Neurobiol Aging. 2018 Jun;66:12-22. doi: 10.1016/j.neurobiolaging.2018.02.003. Epub 2018 Feb 10.
Dopaminergic medications improve the motor symptoms of Parkinson's disease (PD), but their effect on response inhibition, a critical executive function, remains unclear. Previous studies primarily enrolled patients in more advanced stages of PD, when dopaminergic medication loses efficacy, and patients were typically on multiple medications. Here, we recruited 21 patients in early-stage PD on levodopa monotherapy and 37 age-matched controls to perform the stop-signal task during functional magnetic resonance imaging. In contrast to previous studies reporting null effects in more advanced PD, levodopa significantly improved response inhibition performance in our sample. No significant group differences were found in brain activations to pure motor inhibition or error processing (stop success vs. error trials). However, relative to controls, the PD group showed weaker striatal activations to salient events (infrequent vs. frequent events: stop vs. go trials) and fronto-striatal task-residual functional connectivity; both were restored with levodopa. Thus, levodopa appears to improve an important executive function in early-stage PD via enhanced salient signal processing, shedding new light on the role of dopaminergic signaling in response inhibition.
多巴胺能药物可改善帕金森病 (PD) 的运动症状，但它们对反应抑制（一种关键的执行功能）的影响仍不清楚。以前的研究主要招募处于 PD 更晚期的患者，此时多巴胺能药物失去疗效，且患者通常同时服用多种药物。在这里，我们招募了 21 名接受左旋多巴单一疗法治疗的早期 PD 患者和 37 名年龄匹配的对照者，在功能磁共振成像期间执行停止信号任务。与之前在更晚期 PD 中报告无显著效果的研究相反，左旋多巴显著改善了我们样本中的反应抑制表现。在纯运动抑制或错误处理（停止成功与错误试验）的大脑激活方面，未发现组间存在显著差异。然而，与对照组相比，PD 组在显著事件（罕见与频繁事件：停止与进行试验）和额纹状体任务残余功能连接方面的纹状体激活较弱；服用左旋多巴后，这两种情况均得到恢复。因此，左旋多巴似乎通过增强显著信号处理来改善早期 PD 中的一项重要执行功能，这为多巴胺能信号在反应抑制中的作用提供了新的认识。
